Schwann cells are considered to play a critical role in nerve regeneration. There are many diseases associated with nerve defects and dysfunction of Schwann cells. If autologous Schwann cells can be transplanted, it is expected to be ideal regenerative medicine treatment for these diseases. In fact, treatment by autologous nerve grafting or by a method comprising separating Schwann cells from autologous nerves and culturing and transplanting the Schwann cells is effective for nerve damage due to external injury or removal of malignant tumors. However, harvesting of nerves is extremely invasive to patients, and secondary nerve damage is unavoidable. Further, the number of Schwann cells provided is often insufficient.
Non-patent Literature (NPL) 1 and 2 disclose a method for differentiating Schwann-cell-like cells (dADSC) by using mesenchymal stem cells, such as undifferentiated adipose-derived stem cells (ADSC) (also referred to as “adipose-derived stromal cells”), as a starting material. However, since this method inherently has a risk of external infection, quality control is not easy and the method is problematically costly and time-consuming. It has also been noted that the obtained cells are different from true Schwann cells in traits and functions. Further, Schwann cells created by these methods are not reported to have myelinating ability and may be unable to contribute to saltatory conduction.
Recent research shows that cardiomyocytes, hepatocytes, etc. can be directly induced from fibroblasts (direct reprogramming or direct conversion). If Schwann cells can be directly created from somatic cells, such as fibroblasts, which can be harvested from patients in a low-invasive manner, this will lead to a new low-invasive technique for creating autologous Schwann cells for transplantation with a low risk of oncogenesis.
The following, for example, has been reported regarding the technique of introducing a group of genes of tissue-specific transcription factors into somatic cells to induce direct differentiation into the intended tissue cells without passing through iPS cells (direct reprogramming (direct conversion)):
mouse fibroblasts→chondrocytes (introduction of SOX9+Klf4+c-Myc genes);
mouse fibroblasts→cardiomyocyte (introduction of GATA4+Mef2c+Tbx5 genes);
mouse fibroblasts→hepatocytes (introduction of Hnf4α+(Foxa1 or Foxa2 or Foxa3) genes);
mouse fibroblasts→neural stem cells (for example, introduction of Sox2+FoxG1 genes); and
mouse cells or human cells→hematopoietic stem cells; etc.
However, there have been no reports demonstrating direct conversion of somatic cells into Schwann cells.